Detection of sound and head movement requires mechanoelectrical transduction (MET) channels at tips of hair-cell stereocilia. In vertebrates, the transmembrane channel-like (TMC) proteins TMC1 and TMC2 fulfill critical roles in MET, and substantial evidence implicates these TMCs as subunits of the MET channel. To identify developmental and functional roles of this Tmc subfamily in the zebrafish inner ear, we tested the effects of truncating mutations in tmc1, tmc2a, and tmc2b on in vivo mechanosensation at the onset of hearing and balance, before gender differentiation. We find that tmc1/2a/2b triple-mutant larvae cannot detect sound or orient with respect to gravity. They lack acoustic-evoked behavioral responses, vestibularinduced eye movements, and hair-cell activity as assessed with FM dye labeling and microphonic potentials. Despite complete loss of hair-cell function, tmc triple-mutant larvae retain normal gross morphology of hair bundles and proper trafficking of known MET components Protocadherin 15a (Pcdh15a), Lipoma HMGIC fusion partner-like 5 (Lhfpl5), and Transmembrane inner ear protein (Tmie). Transgenic, hair cell-specific expression of Tmc2b-mEGFP rescues the behavioral and physiological deficits in tmc triple mutants. Results from tmc single and double mutants evince a principle role for Tmc2a and Tmc2b in hearing and balance, respectively, whereas Tmc1 has lower overall impact. Our experiments reveal that, in developing cristae, hair cells stratify into an upper, Tmc2a-dependent layer of teardrop-shaped cells and a lower, Tmc1/2b-dependent tier of gourd-shaped cells. Collectively, our genetic evidence indicates that auditory/vestibular end organs and subsets of hair cells therein rely on distinct combinations of Tmc1/2a/2b.

Objectives/Hypothesis: From the 1970s-1990s the U.S. Smokeless Tobacco Company (USST) conducted aggressive campaigns to solicit college students to buy their smokeless tobacco (ST) products. The scope, scale, methods, and impact of this youth marketing campaign have yet to be analyzed in the academic literature.Study Design: Historical research study. Methods: Internal industry documents describing the USST campaigns were obtained via the University of California, San Francisco's repository of tobacco company records. Marketing materials were obtained from Stanford University's Research Into the Impact of Tobacco Advertising (SRITA) collection of 657 USST advertisements.Results: USST's College Marketing Program (1978 sponsored events in some 350 campuses and hired student representatives in at least 175 colleges and universities across America. College representatives were trained to provide free samples to fellow students. Over a typical school year approximately a quarter million Happy Days, Skoal, and Skoal Bandits samples were handed out to undergraduates. USST paid their student representatives well and offered them a variety of incentives based upon sales growth. During the 1990s, USST's Skoal Music program engaged students on campuses and at "spring break" venues such as Daytona Beach.Conclusions: Targeting of college students on campus was a common tobacco industry practice between the 1940s and early 1960s. From the 1970s through 1990s USST resurrected the method and pursued it with vigor including: distribution of free samples; sponsored events and concerts, branded intramural teams; visits by sports celebrities; logo wearables and merchandise; contests and incentives; and displays and promotions in stores on and surrounding campuses.

The purpose of this study was to assess the effect of a cognitive task on motor cortex excitability and inhibition. Transcranial magnetic stimulation of the motor cortex was performed on 20 healthy individuals (18-24 years; 9 females) to measure motor evoked potentials (MEPs) and cortical silent periods at baseline, during, and following a secondary cognitive task. The MEP amplitude increased from 0.50 ± 0.09-0.87 ± 0.50 mV during a secondary cognitive task (p = .04), and returned to baseline (0.48 ± 0.31 mV; p = .90) posttask. The CSP duration also increased from 93.48 ± 28.76-113.6 ± 33.68 ms (p = .001) during the cognitive task, and returned to baseline posttask (89.0 ± 6.9 ms; p = .88). In the presence of a cognitive task, motor cortex excitability and inhibition were both increased relative to baseline. The increase in inhibition may help to explain the motor deficits experienced while performing a secondary cognitive task.

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